Q92574 (TSC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hamartin

Alternative name(s):
Tuberous sclerosis 1 protein

Gene names

Name:	TSC1
Synonyms:	KIAA0243, TSC

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1164 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Seems not to be required for TSC2 GAP activity towards RHEB. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling. Ref.10 Ref.11
Subunit structure	Interacts with TSC2, leading to stabilize TSC2. In the absence of TSC2, TSC1 self-aggregates. Interacts with DOCK7. Interacts with FBXW5 and TBC1D7. Ref.7 Ref.8 Ref.9 Ref.12 Ref.13 Ref.14 Ref.16
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein. Note: At steady state found in association with membranes. Ref.7
Tissue specificity	Highly expressed in skeletal muscle, followed by heart, brain, placenta, pancreas, lung, liver and kidney. Also expressed in embryonic kidney cells.
Domain	The C-terminal putative coiled-coil domain is necessary for interaction with TSC2.
Post-translational modification	Phosphorylation at Ser-505 does not affect interaction with TSC2.
Involvement in disease	Tuberous sclerosis 1 (TSC1) [MIM:191100]: An autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. It is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical manifestations include epilepsy, learning difficulties, behavioral problems, and skin lesions. Seizures can be intractable and premature death can occur from a variety of disease-associated causes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21 Ref.23 Ref.25 Ref.26 Ref.28 Focal cortical dysplasia of Taylor balloon cell type (FCDBC) [MIM:607341]: Subtype of cortical displasias linked to chronic intractable epilepsy. Cortical dysplasias display a broad spectrum of structural changes, which appear to result from changes in proliferation, migration, differentiation, and apoptosis of neuronal precursors and neurons during cortical development. Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.29

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Epilepsy Tumor suppressor
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of Rho GTPase activity Inferred from direct assay PubMed 10806479. Source: UniProtKB cardiac muscle cell differentiation Inferred from electronic annotation. Source: Compara cell cycle arrest Traceable author statement. Source: Reactome cell projection organization Inferred from electronic annotation. Source: Compara cell-matrix adhesion Inferred from mutant phenotype PubMed 10806479. Source: UniProtKB cerebral cortex development Inferred from electronic annotation. Source: Compara hippocampus development Inferred from electronic annotation. Source: Compara insulin receptor signaling pathway Traceable author statement. Source: Reactome kidney development Inferred from electronic annotation. Source: Compara myelination Inferred from electronic annotation. Source: Compara negative regulation of TOR signaling cascade Inferred from mutant phenotype PubMed 17308101. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype PubMed 10915759. Source: UniProtKB negative regulation of cell size Inferred from electronic annotation. Source: Compara negative regulation of translation Inferred from mutant phenotype PubMed 17308101. Source: UniProtKB neural tube closure Inferred from electronic annotation. Source: Compara positive regulation of focal adhesion assembly Inferred from direct assay PubMed 10806479. Source: UniProtKB potassium ion transport Inferred from electronic annotation. Source: Compara protein heterooligomerization Inferred from electronic annotation. Source: Compara protein stabilization Inferred from direct assay PubMed 11175345. Source: UniProtKB rRNA export from nucleus Inferred from mutant phenotype PubMed 17308101. Source: UniProtKB regulation of phosphoprotein phosphatase activity Inferred from mutant phenotype PubMed 17308101. Source: UniProtKB regulation of protein kinase activity Inferred from electronic annotation. Source: Compara regulation of stress fiber assembly Inferred from direct assay PubMed 10806479. Source: UniProtKB synapse organization Inferred from electronic annotation. Source: Compara
Cellular_component	TSC1-TSC2 complex Inferred from direct assay Ref.8. Source: UniProtKB cell cortex Inferred from direct assay PubMed 10806479. Source: UniProtKB cytoskeletal part Inferred from electronic annotation. Source: Compara growth cone Inferred from electronic annotation. Source: Compara intracellular membrane-bounded organelle Inferred from electronic annotation. Source: Compara lamellipodium Inferred from direct assay PubMed 10806479. Source: UniProtKB membrane Inferred from direct assay PubMed 16636147. Source: UniProtKB
Molecular_function	GTPase regulator activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IKBKB	O14920	3	EBI-1047085,EBI-81266
MAPK14	Q16539	2	EBI-1047085,EBI-73946
NGFRAP1	Q00994	5	EBI-1047085,EBI-741753
TSC2	P49815	7	EBI-1047085,EBI-396587

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q92574-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q92574-2)

The sequence of this isoform differs from the canonical sequence as follows:
     70-120: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1164	1164	Hamartin		PRO_0000065651
Regions
	Coiled coil	721 – 997	277	Potential
	Compositional bias	1034 – 1037	4	Poly-Gly
	Compositional bias	1038 – 1043	6	Poly-Ser
Amino acid modifications
	Modified residue	394	1	Phosphoserine By similarity
	Modified residue	505	1	Phosphoserine Ref.12 Ref.18 Ref.19
	Modified residue	511	1	Phosphoserine Ref.18
	Modified residue	598	1	Phosphoserine Ref.18
Natural variations
	Alternative sequence	70 – 120	51	Missing in isoform 2.		VSP_042890
	Natural variant	51	1	E → D in TSC1; unknown pathological significance.		VAR_009397
	Natural variant	68	1	H → R in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. Ref.30		VAR_054386
	Natural variant	72	1	L → P in TSC1. Ref.23		VAR_054387
	Natural variant	158	1	F → C in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. Ref.30		VAR_054388
	Natural variant	190	1	R → S.		VAR_009398
	Natural variant	191	1	L → H in TSC1; unknown pathological significance.		VAR_009399
	Natural variant	198 – 199	2	NF → I in TSC1.		VAR_009400
	Natural variant	206	1	H → D in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. Ref.30		VAR_054389
	Natural variant	216	1	F → L in a bladder tumor; diffuse punctate cytoplasmic distribution in aminoacid-starved conditions; does not affect interaction with TSC2. Ref.30		VAR_054390
	Natural variant	224	1	M → R in TSC1; unknown pathological significance.		VAR_009401
	Natural variant	322	1	M → T. Ref.21 Ref.22 Ref.24 Ref.25 Ref.27 Corresponds to variant rs1073123 [ dbSNP | Ensembl ].		VAR_009402
	Natural variant	417	1	T → I in TSC1; unknown pathological significance; does not affect interaction with TSC2. Ref.25 Ref.27 Ref.30		VAR_009403
	Natural variant	500	1	R → Q in TSC1. Ref.28		VAR_054391
	Natural variant	577	1	E → D. Ref.27		VAR_009404
	Natural variant	586 – 589	4	CKIP → S in TSC1.		VAR_009405
	Natural variant	587	1	K → R. Ref.1 Ref.22		VAR_009406
	Natural variant	654	1	Q → E in TSC1. Ref.25		VAR_009407
	Natural variant	726	1	A → E in TSC1. Ref.21		VAR_009408
	Natural variant	732	1	H → Y in FCDBC; unknown pathological significance. Ref.21 Ref.22 Ref.24 Ref.29		VAR_009409
	Natural variant	809	1	E → Q. Ref.24		VAR_009410
	Natural variant	829	1	S → R. Ref.27		VAR_009411
	Natural variant	899	1	T → S in TSC1. Ref.25		VAR_009412
	Natural variant	1035	1	G → S. Ref.21 Ref.22		VAR_009413
	Natural variant	1108	1	G → S. Ref.22		VAR_009414

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 2. Checksum: EF15509385C7AACC	FASTA	1,164	129,767
	10 20 30 40 50 60 MAQQANVGEL LAMLDSPMLG VRDDVTAVFK ENLNSDRGPM LVNTLVDYYL ETSSQPALHI 70 80 90 100 110 120 LTTLQEPHDK HLLDRINEYV GKAATRLSIL SLLGHVIRLQ PSWKHKLSQA PLLPSLLKCL 130 140 150 160 170 180 KMDTDVVVLT TGVLVLITML PMIPQSGKQH LLDFFDIFGR LSSWCLKKPG HVAEVYLVHL 190 200 210 220 230 240 HASVYALFHR LYGMYPCNFV SFLRSHYSMK ENLETFEEVV KPMMEHVRIH PELVTGSKDH 250 260 270 280 290 300 ELDPRRWKRL ETHDVVIECA KISLDPTEAS YEDGYSVSHQ ISARFPHRSA DVTTSPYADT 310 320 330 340 350 360 QNSYGCATST PYSTSRLMLL NMPGQLPQTL SSPSTRLITE PPQATLWSPS MVCGMTTPPT 370 380 390 400 410 420 SPGNVPPDLS HPYSKVFGTT AGGKGTPLGT PATSPPPAPL CHSDDYVHIS LPQATVTPPR 430 440 450 460 470 480 KEERMDSARP CLHRQHHLLN DRGSEEPPGS KGSVTLSDLP GFLGDLASEE DSIEKDKEEA 490 500 510 520 530 540 AISRELSEIT TAEAEPVVPR GGFDSPFYRD SLPGSQRKTH SAASSSQGAS VNPEPLHSSL 550 560 570 580 590 600 DKLGPDTPKQ AFTPIDLPCG SADESPAGDR ECQTSLETSI FTPSPCKIPP PTRVGFGSGQ 610 620 630 640 650 660 PPPYDHLFEV ALPKTAHHFV IRKTEELLKK AKGNTEEDGV PSTSPMEVLD RLIQQGADAH 670 680 690 700 710 720 SKELNKLPLP SKSVDWTHFG GSPPSDEIRT LRDQLLLLHN QLLYERFKRQ QHALRNRRLL 730 740 750 760 770 780 RKVIKAAALE EHNAAMKDQL KLQEKDIQMW KVSLQKEQAR YNQLQEQRDT MVTKLHSQIR 790 800 810 820 830 840 QLQHDREEFY NQSQELQTKL EDCRNMIAEL RIELKKANNK VCHTELLLSQ VSQKLSNSES 850 860 870 880 890 900 VQQQMEFLNR QLLVLGEVNE LYLEQLQNKH SDTTKEVEMM KAAYRKELEK NRSHVLQQTQ 910 920 930 940 950 960 RLDTSQKRIL ELESHLAKKD HLLLEQKKYL EDVKLQARGQ LQAAESRYEA QKRITQVFEL 970 980 990 1000 1010 1020 EILDLYGRLE KDGLLKKLEE EKAEAAEAAE ERLDCCNDGC SDSMVGHNEE ASGHNGETKT 1030 1040 1050 1060 1070 1080 PRPSSARGSS GSRGGGGSSS SSSELSTPEK PPHQRAGPFS SRWETTMGEA SASIPTTVGS 1090 1100 1110 1120 1130 1140 LPSSKSFLGM KARELFRNKS ESQCDEDGMT SSLSESLKTE LGKDLGVEAK IPLNLDGPHP 1150 1160 SPPTPDSVGQ LHIMDYNETH HEHS
	Isoform 2 [UniParc]. Checksum: 6EA012443870A73C	FASTA	1,113	124,015
	10 20 30 40 50 60 MAQQANVGEL LAMLDSPMLG VRDDVTAVFK ENLNSDRGPM LVNTLVDYYL ETSSQPALHI 70 80 90 100 110 120 LTTLQEPHDK MDTDVVVLTT GVLVLITMLP MIPQSGKQHL LDFFDIFGRL SSWCLKKPGH 130 140 150 160 170 180 VAEVYLVHLH ASVYALFHRL YGMYPCNFVS FLRSHYSMKE NLETFEEVVK PMMEHVRIHP 190 200 210 220 230 240 ELVTGSKDHE LDPRRWKRLE THDVVIECAK ISLDPTEASY EDGYSVSHQI SARFPHRSAD 250 260 270 280 290 300 VTTSPYADTQ NSYGCATSTP YSTSRLMLLN MPGQLPQTLS SPSTRLITEP PQATLWSPSM 310 320 330 340 350 360 VCGMTTPPTS PGNVPPDLSH PYSKVFGTTA GGKGTPLGTP ATSPPPAPLC HSDDYVHISL 370 380 390 400 410 420 PQATVTPPRK EERMDSARPC LHRQHHLLND RGSEEPPGSK GSVTLSDLPG FLGDLASEED 430 440 450 460 470 480 SIEKDKEEAA ISRELSEITT AEAEPVVPRG GFDSPFYRDS LPGSQRKTHS AASSSQGASV 490 500 510 520 530 540 NPEPLHSSLD KLGPDTPKQA FTPIDLPCGS ADESPAGDRE CQTSLETSIF TPSPCKIPPP 550 560 570 580 590 600 TRVGFGSGQP PPYDHLFEVA LPKTAHHFVI RKTEELLKKA KGNTEEDGVP STSPMEVLDR 610 620 630 640 650 660 LIQQGADAHS KELNKLPLPS KSVDWTHFGG SPPSDEIRTL RDQLLLLHNQ LLYERFKRQQ 670 680 690 700 710 720 HALRNRRLLR KVIKAAALEE HNAAMKDQLK LQEKDIQMWK VSLQKEQARY NQLQEQRDTM 730 740 750 760 770 780 VTKLHSQIRQ LQHDREEFYN QSQELQTKLE DCRNMIAELR IELKKANNKV CHTELLLSQV 790 800 810 820 830 840 SQKLSNSESV QQQMEFLNRQ LLVLGEVNEL YLEQLQNKHS DTTKEVEMMK AAYRKELEKN 850 860 870 880 890 900 RSHVLQQTQR LDTSQKRILE LESHLAKKDH LLLEQKKYLE DVKLQARGQL QAAESRYEAQ 910 920 930 940 950 960 KRITQVFELE ILDLYGRLEK DGLLKKLEEE KAEAAEAAEE RLDCCNDGCS DSMVGHNEEA 970 980 990 1000 1010 1020 SGHNGETKTP RPSSARGSSG SRGGGGSSSS SSELSTPEKP PHQRAGPFSS RWETTMGEAS 1030 1040 1050 1060 1070 1080 ASIPTTVGSL PSSKSFLGMK ARELFRNKSE SQCDEDGMTS SLSESLKTEL GKDLGVEAKI 1090 1100 1110 PLNLDGPHPS PPTPDSVGQL HIMDYNETHH EHS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34." van Slegtenhorst M.A., de Hoogt R., Hermans C., Nellist M., Janssen B., Verhoef S., Lindhout D., van den Ouweland A.M.W., Halley D.J.J., Young J., Burley M., Jeremiah S., Woodward K., Nahmias J., Fox M., Ekong R., Osborne J., Wolfe J. , Povey S., Snell R.G., Cheadle J.P., Jones A.C., Tachataki M., Ravine D., Sampson J.R., Reeve M.P., Richardson P., Wilmer F., Munro C., Hawkins T.L., Sepp T., Ali J.B.M., Ward S., Green A.J., Yates J.R.W., Kwiatkowska J., Henske E.P., Short M.P., Haines J.H., Jozwiak S., Kwiatkowski D.J. Science 277:805-808(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-587.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N. DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 466-1164 (ISOFORM 1/2). Tissue: Bone marrow.
[6]	"A silent mutation 1947 T-->C in exon 15 of TSC1 in Chinese." Fang L., Wang N., Murong S.X., Wu Z.Y., Lin M.T. Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 568-586.
[7]	"Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles." Plank T.L., Yeung R.S., Henske E.P. Cancer Res. 58:4766-4770(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH TSC2.
[8]	"Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products." van Slegtenhorst M.A., Nellist M., Nagelkerken B., Cheadle J.P., Snell R.G., van den Ouweland A.M.W., Reuser A., Sampson J.R., Halley D.J.J., van der Sluijs P. Hum. Mol. Genet. 7:1053-1057(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TSC2.
[9]	"Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin." Nellist M., van Slegtenhorst M.A., Goedbloed M., van den Ouweland A.M.W., Halley D.J.J., van der Sluijs P. J. Biol. Chem. 274:35647-35652(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TSC2.
[10]	"Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling." Tee A.R., Fingar D.C., Manning B.D., Kwiatkowski D.J., Cantley L.C., Blenis J. Proc. Natl. Acad. Sci. U.S.A. 99:13571-13576(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity." Li Y., Inoki K., Guan K.-L. Mol. Cell. Biol. 24:7965-7975(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Phosphorylation and binding partner analysis of the TSC1-TSC2 complex." Nellist M., Burgers P.C., van den Ouweland A.M.W., Halley D.J.J., Luider T.M. Biochem. Biophys. Res. Commun. 333:818-826(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-505, MASS SPECTROMETRY, INTERACTION WITH DOCK7 AND TSC2.
[13]	"TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase." Chong-Kopera H., Inoki K., Li Y., Zhu T., Garcia-Gonzalo F.R., Rosa J.L., Guan K.-L. J. Biol. Chem. 281:8313-8316(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TSC2.
[14]	"Identification of TBC7 having TBC domain as a novel binding protein to TSC1-TSC2 complex." Nakashima A., Yoshino K., Miyamoto T., Eguchi S., Oshiro N., Kikkawa U., Yonezawa K. Biochem. Biophys. Res. Commun. 361:218-223(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TBC1D7.
[15]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[16]	"WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase." Hu J., Zacharek S., He Y.J., Lee H., Shumway S., Duronio R.J., Xiong Y. Genes Dev. 22:866-871(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FBXW5.
[17]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Platelet.
[18]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505; SER-511 AND SER-598, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[20]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]	"Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis." Jones A.C., Daniells C.E., Snell R.G., Tachataki M., Idziaszczyk S.A., Krawczak M., Sampson J.R., Cheadle J.P. Hum. Mol. Genet. 6:2155-2161(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TSC1 GLU-726, VARIANTS THR-322; TYR-732 AND SER-1035. Tissue: Peripheral blood.
[22]	"Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance." Kwiatkowska J., Jozwiak S., Hall F., Henske E.P., Haines J.L., McNamara P., Braiser J., Wigowska-Sowinska J., Kasprzyk-Obara J., Short M.P., Kwiatkowski D.J. Ann. Hum. Genet. 62:277-285(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THR-322; ARG-587; TYR-732; SER-1035 AND SER-1108. Tissue: Blood.
[23]	"Protein truncation test for screening hamartin gene mutations and report of new disease-causing mutations." Benit P., Kara-Mostefa A., Hadj-Rabia S., Munnich A., Bonnefont J.-P. Hum. Mutat. 14:428-432(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TSC1 PRO-72.
[24]	"Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis." Niida Y., Lawrence-Smith N., Banwell A., Hammer E., Lewis J., Beauchamp R.L., Sims K., Ramesh V., Ozelius L. Hum. Mutat. 14:412-422(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THR-322; TYR-732 AND GLN-809. Tissue: Blood and Lymphoblast.
[25]	"Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex." Zhang H., Nanba E., Yamamoto T., Ninomiya H., Ohno K., Mizuguchi M., Takeshita K. J. Hum. Genet. 44:391-396(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TSC1 ILE-417; GLU-654 AND SER-899, VARIANT THR-322. Tissue: Blood.
[26]	"Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation." Van Slegtenhorst M.A., Verhoef S., Tempelaars A., Bakker L., Wang Q., Wessels M., Bakker R., Nellist M., Lindhout D., Halley D.J.J., van den Ouweland A.M.W. J. Med. Genet. 36:285-289(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TSC1, VARIANTS. Tissue: Peripheral blood.
[27]	"Analysis of all exons of TSC1 and TSC2 genes for germline mutations in Japanese patients with tuberous sclerosis: report of 10 mutations." Yamashita Y., Ono J., Okada S., Wataya-Kaneda M., Yoshikawa K., Nishizawa M., Hirayama Y., Kobayashi E., Seyama K., Hino O. Am. J. Med. Genet. 90:123-126(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THR-322; ILE-417; ASP-577 AND ARG-829. Tissue: Peripheral blood leukocyte.
[28]	"Tuberous sclerosis type 1: three novel mutations detected in exon 15 by a combination of HDA and TGGE." Hass J., Mayer K., Rott H.-D. Hum. Mutat. 16:88-88(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TSC1 GLN-500.
[29]	"Focal cortical dysplasia of Taylor's balloon cell type: mutational analysis of the TSC1 gene indicates a pathogenic relationship to tuberous sclerosis." Becker A.J., Urbach H., Scheffler B., Baden T., Normann S., Lahl R., Pannek H.W., Tuxhorn I., Elger C.E., Schramm J., Wiestler O.D., Bluemcke I. Ann. Neurol. 52:29-37(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FCDBC TYR-732.
[30]	"Bladder tumour-derived somatic TSC1 missense mutations cause loss of function via distinct mechanisms." Pymar L.S., Platt F.M., Askham J.M., Morrison E.E., Knowles M.A. Hum. Mol. Genet. 17:2006-2017(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARG-68; CYS-158; ASP-206; LEU-216 AND ILE-417, CHARACTERIZATION OF VARIANTS ARG-68; CYS-158; ASP-206; LEU-216 AND ILE-417.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Tuberous sclerosis database Tuberous sclerosis 1 (TSC1)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF013168 mRNA. Translation: AAC51674.1. AK303030 mRNA. Translation: BAH13883.1. AL445645 Genomic DNA. Translation: CAH72112.1. CH471090 Genomic DNA. Translation: EAW88021.1. AC002096 Genomic DNA. No translation available. D87683 mRNA. Translation: BAA13436.1. AF234185 Genomic DNA. Translation: AAF61948.1.
IPI	IPI00022043. IPI00921907.
PIR	T03814.
RefSeq	NP_000359.1. NM_000368.4. NP_001155898.1. NM_001162426.1. NP_001155899.1. NM_001162427.1.
UniGene	Hs.370854.
3D structure databases
ProteinModelPortal	Q92574.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92574. 31 interactions.
MINT	MINT-1534928.
STRING	9606.ENSP00000298552.
PTM databases
PhosphoSite	Q92574.
Polymorphism databases
DMDM	9297077.
Proteomic databases
PaxDb	Q92574.
PRIDE	Q92574.
Protocols and materials databases
DNASU	7248.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000298552; ENSP00000298552; ENSG00000165699. ENST00000440111; ENSP00000394524; ENSG00000165699. ENST00000545250; ENSP00000444017; ENSG00000165699.
GeneID	7248.
KEGG	hsa:7248.
UCSC	uc004cca.2. human. uc011mcq.1. human.
Organism-specific databases
CTD	7248.
GeneCards	GC09M135766.
HGNC	HGNC:12362. TSC1.
HPA	CAB011568. CAB012481.
MIM	191100. phenotype. 605284. gene. 607341. phenotype.
neXtProt	NX_Q92574.
Orphanet	65683. Isolated focal cortical dysplasia. 538. Lymphangioleiomyomatosis. 805. Tuberous sclerosis.
PharmGKB	PA37034.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG68098.
HOGENOM	HOG000232119.
HOVERGEN	HBG012559.
InParanoid	Q92574.
KO	K07206.
OMA	EHNAAMK.
OrthoDB	EOG4S4PFD.
PhylomeDB	Q92574.
Enzyme and pathway databases
Pathway_Interaction_DB	pi3kciaktpathway. Class I PI3K signaling events mediated by Akt. mtor_4pathway. mTOR signaling pathway.
Reactome	REACT_111102. Signal Transduction.
SignaLink	Q92574.
Gene expression databases
ArrayExpress	Q92574.
Bgee	Q92574.
CleanEx	HS_TSC1.
Genevestigator	Q92574.
GermOnline	ENSG00000165699. Homo sapiens.
Family and domain databases
InterPro	IPR007483. Hamartin. [Graphical view]
PANTHER	PTHR15154. PTHR15154. 1 hit.
Pfam	PF04388. Hamartin. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TSC1. human.
GenomeRNAi	7248.
NextBio	28341.
SOURCE	Search...

Entry information

Entry name

TSC1_HUMAN

Accession

Primary (citable) accession number: Q92574
Secondary accession number(s): B7Z897, Q5VVN5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 1, 1998
Last modified:	May 29, 2013
This is version 128 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.